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Compound Detail

CHEMBL4594350

ADAGRASIB
💊 Approved Drug
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💊 Approved Drug
C=C(F)C(=O)N1CCN(c2nc(OC[C@@H]3CCCN3C)nc3c2CCN(c2cccc4cccc(Cl)c24)C3)C[C@@H]1CC#N

Basic Information

ChEMBL ID CHEMBL4594350
Name ADAGRASIB
Phase Approved
Structure Type MOL
InChI Key PEMUGDMSUDYLHU-ZEQRLZLVSA-N
Therapeutic ✓ Yes

Known Names

Adagrasib Kras g12c inhibitor mrtx849 Krazati Mrtx-849 Mrtx849
11
Targets
28
Activities
3
Assay Types
23
PK Parameters
20
Publications
5
Known Names
6
Indications
1
Mechanisms

Molecular Properties

604.1
MW (Da)
4.73
ALogP
8
HBA
0
HBD
88.8
PSA (Ų)
0.36
QED
1
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2022
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Chemical Probe
USAN Stem -rasib
USAN Year 2021

Extended Properties

Molecular Formula C32H35ClFN7O2
MW 604.13
Aromatic Rings 3
Heavy Atoms 43
NP-Likeness -0.81

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
GTPase KRas inhibitor INHIBITOR GTPase KRas

Indications

Carcinoma, Non-Small-Cell Lung Neoplasms Colorectal Neoplasms Lung Neoplasms Neoplasm Metastasis Pancreatic Neoplasms

ATC Classification

L01XX77
adagrasib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 20 meas. best 9.0
EC50 6 meas. best 8.0
Ki 2 meas. best 5.43

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
NCI-H358
CHEMBL614135
IC50 9.0 8.236 1.0 5
CDK7/Cyclin H/MNAT1
CHEMBL3038473
IC50 8.89 8.89 1.3 1
MIA PaCa-2
CHEMBL614725
IC50 8.41 7.7775 3.9 4
GTPase KRas
CHEMBL2189121
IC50 8.3 8.1125 5.0 4
GTPase KRas
CHEMBL2189121
EC50 8.0 8.0 10.0 1
Unchecked
CHEMBL612545
IC50 7.85 7.85 14.0 1
SOS1-KRAS
CHEMBL5465393
IC50 6.89 6.89 130.0 1
von Hippel-Lindau disease tumor suppressor/KRAS
CHEMBL5169273
EC50 6.6 6.6 250.0 5
AGS
CHEMBL613860
IC50 5.85 5.85 1400.0 1
PaTu 8988t
CHEMBL4296488
IC50 5.52 5.52 3000.0 1
GTPase KRas
CHEMBL2189121
Ki 5.43 5.43 3700.0 2
NCI-H1975
CHEMBL614348
IC50 5.2 5.2 6370.0 1
A549
CHEMBL392
IC50 4.89 4.89 12900.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 15900.0 ng.hr.mL-1 Mus musculus
AUC 4470.0 ng.hr.mL-1 Canis lupus familiaris
AUC 2670.0 ng.hr.mL-1 Rattus norvegicus
CL 19.9 mL.min-1.kg-1 Mus musculus
CL 29.6 mL.min-1.kg-1 Canis lupus familiaris
CL 44.2 mL.min-1.kg-1 Rattus norvegicus
CL 215.0 mL.min-1.g-1 Homo sapiens
CL 80.0 mL.min-1.g-1 Homo sapiens
Cmax 3989.21 nM Mus musculus
Cmax 417.13 nM Canis lupus familiaris
Cmax 345.95 nM Rattus norvegicus
F 62.9 % Mus musculus
F 25.9 % Canis lupus familiaris
F 29.7 % Rattus norvegicus
T1/2 1.51 hr Mus musculus
T1/2 7.56 hr Canis lupus familiaris
T1/2 50.0 hr Mus musculus
T1/2 50.0 hr Canis lupus familiaris
T1/2 50.0 hr Homo sapiens
T1/2 2.57 hr Rattus norvegicus
Tmax 1.0 hr Mus musculus
Tmax 4.0 hr Canis lupus familiaris
Tmax 2.67 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
NCI-H358 IC50 = 1.0 nM 9.0 Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C muta... 36621179
CDK7/Cyclin H/MNAT1 IC50 = 1.3 nM 8.89 Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) in leukemia cells 36561076
MIA PaCa-2 IC50 = 3.92 nM 8.41 Antiproliferative activity against human MIA PaCa-2 cells assessed as inhibition... 37393576
MIA PaCa-2 IC50 = 4.0 nM 8.4 Antiproliferative activity against human MIA PaCa-2 cells assessed as reduction ... 34965125
GTPase KRas IC50 = 5.0 nM 8.3 Inhibition of KRAS G12C mutant in human NCI-H358 cells assessed as reduction in ... 39137454
GTPase KRas IC50 = 5.0 nM 8.3 Inhibition of KRAS G12C mutant in human MIAPaCa2 cells assessed as reduction in ... 32250617
NCI-H358 IC50 = 6.0 nM 8.22 Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C muta... 37395055
NCI-H358 IC50 = 6.0 nM 8.22 Antiproliferative activity against human NCI-H358 cells assessed as reduction in... 34965125
NCI-H358 IC50 = 9.2 nM 8.04 Antiproliferative activity against human NCI-H358 cells harboring KRAS p.G12C mu... 37393576
GTPase KRas EC50 = 10.0 nM 8.0 Inhibition of KRAS (unknown origin) dependent signal transduction 33228976
GTPase KRas IC50 = 10.0 nM 8.0 Inhibition of KRAS G12C mutant in human MIA PaCa-2 cells assessed as reduction i... 32910655
GTPase KRas IC50 = 14.0 nM 7.85 Inhibition of KRAS G12C mutant in human NCI-H358 cells assessed as reduction in ... 32250617
Unchecked IC50 = 14.0 nM 7.85 Inhibition of ERK phosphorylation in human NCI-H358 cells incubated for 3 hrs 37542991
NCI-H358 IC50 = 20.0 nM 7.7 Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C muta... 36395648
MIA PaCa-2 IC50 = 50.0 nM 7.3 Antiproliferative activity against human MIA PaCa-2 cells harboring KRAS G12C mu... 36395648
MIA PaCa-2 IC50 = 100.0 nM 7.0 Antiproliferative activity against human MIA PaCa-2 cells 32910655
SOS1-KRAS IC50 = 130.0 nM 6.89 Inhibition of KRAS G12C mutant/SOS1 (unknown origin) interaction incubated for 2... 36395648
von Hippel-Lindau disease tumor suppressor/KRAS EC50 = 250.0 nM 6.6 PROTAC activity at VHL/KRAS G12C mutant in human NCI- H2030 cells assessed as in... 33189436
von Hippel-Lindau disease tumor suppressor/KRAS EC50 = 250.0 nM 6.6 PROTAC activity at VHL/KRAS G12C mutant in human NCI-H358 cells assessed as indu... 33189436
von Hippel-Lindau disease tumor suppressor/KRAS EC50 = 250.0 nM 6.6 PROTAC activity at VHL/KRAS G12C mutant in human NCI-H23 cells assessed as induc... 33189436

Literature References

Data from ChEMBL 36 via Core Engine